SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury

Dawei Wang,1,* Hongyan Cao,2,* Xu Wang,3 Jinchun Wang,4 Manli Wang,5 Jian Zhang,6 Lin Wang6 1Department of Emergency, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Cardiology, The First Hospital of Jilin University, Changchun, 130021,...

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Autores principales:	Wang D, Cao H, Wang X, Wang J, Wang M, Zhang J, Wang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	exercise myocardial ischemia/reperfusion injury oxidative stress sirt1 Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/01242e17e1ae4b6c9c6b5be405a7599b
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spelling	oai:doaj.org-article:01242e17e1ae4b6c9c6b5be405a7599b2021-12-02T18:13:26ZSIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury1178-7031https://doaj.org/article/01242e17e1ae4b6c9c6b5be405a7599b2021-04-01T00:00:00Zhttps://www.dovepress.com/sirt1-is-required-for-exercise-induced-beneficial-effects-on-myocardia-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Dawei Wang,1,* Hongyan Cao,2,* Xu Wang,3 Jinchun Wang,4 Manli Wang,5 Jian Zhang,6 Lin Wang6 1Department of Emergency, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Cardiology, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 3Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 4Department of Emergency, Jilin Provincial FAW General Hospital, Changchun, 130011, People’s Republic of China; 5Department of Geriatrics, Changchun Central Hospital, Changchun, 130000, People’s Republic of China; 6Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang; Lin WangDepartment of Cardiovascular Center, The First Hospital of Jilin University, No. 71, Xinmin Street, Changchun, 130021, Jilin Province, People’s Republic of ChinaTel +86-0431-88783417Email wanglinjdyy@jlu.edu.cn; Kenny1026@jlu.edu.cnBackground: Exercise training has been regarded as an effective mean of prevention and treatment of cardiovascular diseases (CVD), and exercise can improve the antioxidant capacity of the myocardial. While SIRT1 has been proved to protects the heart from myocardial ischemia/reperfusion (MI/R) injury and apoptosis, less is known about the association between exercise-induced cardioprotection and SIRT1.Methods and Results: MI/R injury model was constructed after swimming training in mice. Significantly reduced myocardial infarct size, decreased apoptosis ratio and upregulated SIRT1 protein expression in heart were found in swam mice by 2,3,5-triphenyltetrazolium chloride (TTC) staining of heart sections, TUNEL staining of frozen sections and Western blotting. The results of TUNEL staining and Western blotting suggested activation of SIRT1 using resveratrol (RSV) or inhibition of SIRT1 using EX527 in vitro blocked or accelerated cardiomyocytes apoptosis which induced by hypoxia/reoxygenation (H/R) respectively and regulated the expression of antioxidants in vitro. PGC-1α has been identified as one of the downstream genes of SIRT1 modulating oxidative stress and apoptosis. Importantly, the data of TTC staining, TUNEL staining, Western blotting, echocardiography and histopathological staining revealed that mice with inducible cardiac SIRT1-knockout blocked the protective effects of exercise preconditioning on myocardial infarct size, myocardial apoptosis, adverse ventricular remodeling, cardiac fibrosis and cardiac dysfunction after MI/R injury, simultaneously exercise-induced expression of myocardial antioxidant stress factors was hindered which was detected by immunohistochemical analysis.Conclusion: SIRT1 protects against oxidative stress after MI/R injury by activating downstream PGC-1α and promoting the production of antioxidant enzymes. SIRT1 is required for exercise to protect against myocardial apoptosis and maladaptive ventricular remodelling induced by myocardial ischemia/reperfusion injury.Keywords: exercise, myocardial ischemia/reperfusion injury, oxidative stress, SIRT1Wang DCao HWang XWang JWang MZhang JWang LDove Medical Pressarticleexercisemyocardial ischemia/reperfusion injuryoxidative stresssirt1PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1283-1296 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exercise myocardial ischemia/reperfusion injury oxidative stress sirt1 Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	exercise myocardial ischemia/reperfusion injury oxidative stress sirt1 Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Wang D Cao H Wang X Wang J Wang M Zhang J Wang L SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury
description	Dawei Wang,1,* Hongyan Cao,2,* Xu Wang,3 Jinchun Wang,4 Manli Wang,5 Jian Zhang,6 Lin Wang6 1Department of Emergency, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Cardiology, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 3Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 4Department of Emergency, Jilin Provincial FAW General Hospital, Changchun, 130011, People’s Republic of China; 5Department of Geriatrics, Changchun Central Hospital, Changchun, 130000, People’s Republic of China; 6Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang; Lin WangDepartment of Cardiovascular Center, The First Hospital of Jilin University, No. 71, Xinmin Street, Changchun, 130021, Jilin Province, People’s Republic of ChinaTel +86-0431-88783417Email wanglinjdyy@jlu.edu.cn; Kenny1026@jlu.edu.cnBackground: Exercise training has been regarded as an effective mean of prevention and treatment of cardiovascular diseases (CVD), and exercise can improve the antioxidant capacity of the myocardial. While SIRT1 has been proved to protects the heart from myocardial ischemia/reperfusion (MI/R) injury and apoptosis, less is known about the association between exercise-induced cardioprotection and SIRT1.Methods and Results: MI/R injury model was constructed after swimming training in mice. Significantly reduced myocardial infarct size, decreased apoptosis ratio and upregulated SIRT1 protein expression in heart were found in swam mice by 2,3,5-triphenyltetrazolium chloride (TTC) staining of heart sections, TUNEL staining of frozen sections and Western blotting. The results of TUNEL staining and Western blotting suggested activation of SIRT1 using resveratrol (RSV) or inhibition of SIRT1 using EX527 in vitro blocked or accelerated cardiomyocytes apoptosis which induced by hypoxia/reoxygenation (H/R) respectively and regulated the expression of antioxidants in vitro. PGC-1α has been identified as one of the downstream genes of SIRT1 modulating oxidative stress and apoptosis. Importantly, the data of TTC staining, TUNEL staining, Western blotting, echocardiography and histopathological staining revealed that mice with inducible cardiac SIRT1-knockout blocked the protective effects of exercise preconditioning on myocardial infarct size, myocardial apoptosis, adverse ventricular remodeling, cardiac fibrosis and cardiac dysfunction after MI/R injury, simultaneously exercise-induced expression of myocardial antioxidant stress factors was hindered which was detected by immunohistochemical analysis.Conclusion: SIRT1 protects against oxidative stress after MI/R injury by activating downstream PGC-1α and promoting the production of antioxidant enzymes. SIRT1 is required for exercise to protect against myocardial apoptosis and maladaptive ventricular remodelling induced by myocardial ischemia/reperfusion injury.Keywords: exercise, myocardial ischemia/reperfusion injury, oxidative stress, SIRT1
format	article
author	Wang D Cao H Wang X Wang J Wang M Zhang J Wang L
author_facet	Wang D Cao H Wang X Wang J Wang M Zhang J Wang L
author_sort	Wang D
title	SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury
title_short	SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury
title_full	SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury
title_fullStr	SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury
title_full_unstemmed	SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury
title_sort	sirt1 is required for exercise-induced beneficial effects on myocardial ischemia/reperfusion injury
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/01242e17e1ae4b6c9c6b5be405a7599b
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SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury

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